Afficher la notice abrégée

Carboxylate-functionalized foldamer inhibitors of HIV-1 integrase and Topoisomerase 1: artificial analogues of DNA mimic proteins

dc.rights.licenseopenen_US
dc.contributor.authorCORVAGLIA, Valentina
dc.contributor.authorCARBAJO, Daniel
dc.contributor.authorPRABHAKARAN, Panchami
dc.contributor.authorZIACH, Krzysztof
dc.contributor.authorKUMAR MANDAL, Pradeep
hal.structure.identifierSanofi-Aventis R&D
dc.contributor.authorSANTOS, Victor
hal.structure.identifierSanofi-Aventis R&D
dc.contributor.authorLEGEAY, Carole
hal.structure.identifierSanofi-Aventis R&D
dc.contributor.authorVOGEL, Rachel
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorPARISSI, Vincent
dc.contributor.authorPOURQUIER, Philippe
dc.contributor.authorHUC, Ivan
dc.date.accessioned2023-06-14T06:46:02Z
dc.date.available2023-06-14T06:46:02Z
dc.date.issued2019-06-20
dc.identifier.issn0305-1048en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/182669
dc.description.abstractEnInspired by DNA mimic proteins, we have introduced aromatic foldamers bearing phosphonate groups as synthetic mimics of the charge surface of B-DNA and competitive inhibitors of some therapeutically relevant DNA-binding enzymes: the human DNA Topoisomerase 1 (Top1) and the human HIV-1 integrase (HIV-1 IN). We now report on variants of these anionic foldamers bearing carboxylates instead of phosphonates. Several new monomers have been synthesized with protecting groups suitable for solid phase synthesis (SPS). Six hexadecaamides have been prepared using SPS. Proof of their resemblance to B-DNA was brought by the first crystal structure of one of these DNA-mimic foldamers in its polyanionic form. While some of the foldamers were found to be as active as, or even more active than, the original phosphonate oligomers, others had no activity at all or could even stimulate enzyme activity in vitro. Some foldamers were found to have differential inhibitory effects on the two enzymes. These results demonstrate a strong dependence of inhibitory activity on foldamer structure and charge distribution. They open broad avenues for the development of new classes of derivatives that could inhibit the interaction of specific proteins with their DNA target thereby influencing the cellular pathways in which they are involved.
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/us/*
dc.title.enCarboxylate-functionalized foldamer inhibitors of HIV-1 integrase and Topoisomerase 1: artificial analogues of DNA mimic proteins
dc.typeArticle de revueen_US
dc.identifier.doi10.1093/nar/gkz352en_US
dc.subject.halChimie/Chimie thérapeutiqueen_US
dc.subject.halSciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Biologie structurale [q-bio.BM]en_US
bordeaux.journalNucleic Acids Researchen_US
bordeaux.page5511-5521en_US
bordeaux.volume47en_US
bordeaux.hal.laboratoriesMFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234en_US
bordeaux.issue11en_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcehal
hal.identifierhal-02419418
hal.version1
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccCC BY-NCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Nucleic%20Acids%20Research&rft.date=2019-06-20&rft.volume=47&rft.issue=11&rft.spage=5511-5521&rft.epage=5511-5521&rft.eissn=0305-1048&rft.issn=0305-1048&rft.au=CORVAGLIA,%20Valentina&CARBAJO,%20Daniel&PRABHAKARAN,%20Panchami&ZIACH,%20Krzysztof&KUMAR%20MANDAL,%20Pradeep&rft.genre=article


Fichier(s) constituant ce document

Thumbnail
Nom:
MFP_Nar_2019_Corvaglia.pdf
Taille:
10.98Mo
Format:
PDF
Voir/Ouvrir
Thumbnail
Nom:
license_rdf
Taille:
920octets
Format:
application/rdf+xml
Voir/Ouvrir

Ce document figure dans la(les) collection(s) suivante(s)

Afficher la notice abrégée